Dynamics of TGF-1β and MMP-9 content in the serum of patients with chronic hepatitis C infected with HCV GT1 on the background of antiviral treatment depending on the severity of liver fibrosis
DOI:
https://doi.org/10.14739/2310-1237.2025.2.333017Keywords:
chronic hepatitis C, viral infection, diagnosis, liver fibrosis, cytokines, antiviral therapy, treatmentAbstract
The aim: to analyse the dynamics of TGF-1β and MMP-9 in the blood serum of patients with chronic hepatitis C (HCV) infected with HCV GT1 on the background of antiviral treatment depending on the severity of liver fibrosis.
Materials and methods. The study included 92 patients with GT1 HCV infection treated with antiviral therapy (AVT) – OBV / PTV / r+DSV±RBV. The severity of liver fibrosis was determined by elastometry. The content of TGF-1β (Elabscience, USA) and MMP-9 (Elabscience, USA) in the blood serum was determined by ELISA.
Results. In patients with CHC GT1 before the start of AVT, profibrogenic potential prevailed: increased TGF-1β (p < 0.05), decreased MMP-9 (p < 0.05) and a higher TGF-1β / MMP-9 ratio (p < 0.05). AVT (OBV / PTV / r+DSV±RBV) slows down fibrogenesis and activates antifibrotic processes, which is confirmed by an increase in MMP-9 (p < 0.05) and a decrease in TGF-1β / MMP-9 (p < 0.05) compared to the pre-treatment values. Prior to AVT, patients with GT1 HCV with liver fibrosis F 0–2 had lower MMP-9 levels (p < 0.05) than healthy subjects, with no changes in TGF-1β and TGF-1β / MMP-9 ratio (p > 0.05). In patients with F 3–4 liver fibrosis, serum TGF-1β and the TGF-1β / MMP-9 ratio were higher, and MMP-9 was lower, both compared with healthy subjects (p < 0.05) and compared with patients with F 0–2 (p < 0.05). In patients with F 0–2, at the time of completion of AVT, the studied parameters do not differ from healthy individuals (p > 0.05). In patients with F 3–4 at the time of completion of AVT, the TGF-1β / MMP-9 ratio remains higher both in comparison with healthy individuals (p < 0.05) and in comparison with patients with CHC GT1 with liver fibrosis F 0–2 (p < 0.05).
Conclusions. We demonstrated more significant dynamics of antifibrotic changes during direct-acting antiviral agents based AVT in patients with GT1 CHC in the presence of F 0–2 liver fibrosis compared to patients with F 3–4.
References
Hepatitis C [Internet]. Who.int. [cited 2025 Jun 25]. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
Polaris Observatory HCV Collaborators. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol. 2022;7(5):396-415. doi: https://doi.org/10.1016/s2468-1253(21)00472-6
Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, et al. EASL recommendations on treatment of hepatitis C: Final update of the series☆. J Hepatol. 2020;73(5):1170-218. doi: https://doi.org/10.1016/j.jhep.2020.08.018. Erratum in: J Hepatol. 2023;78(2):452. doi: https://doi.org/10.1016/j.jhep.2022.10.006
Ministry of Health of Ukraine. Pro zatverdzhennia standartiv medychnoi dopomohy pry virusnomu hepatyti C u doroslykh [On approval of standards of medical care for viral hepatitis C in adults]. Order dated 2021 Jan 15 No. 51. Ukrainian. Available from: https://zakon.rada.gov.ua/rada/show/en/v0051282-21#Text
Wedemeyer H, Forns X, Hézode C, Lee SS, Scalori A, Voulgari A, et al. Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies. PLoS One. 2016;11(1):e0145409. doi: https://doi.org/10.1371/journal.pone.0145409
Irekeola AA, Ear EN, Mohd Amin NA, Mustaffa N, Shueb RH. Antivirals against HCV infection: the story thus far. J Infect Dev Ctries. 2022;16(2):231-43. doi: https://doi.org/10.3855/jidc.14485
Gschwantler M, Bamberger T, Graziadei I, Maieron A, Katalinic N, Stauber R. Burden of disease in patients with chronic hepatitis C in the Austrian REAL study. Wien Klin Wochenschr. 2019;131(1-2):8-16. doi: https://doi.org/10.1007/s00508-018-1404-2
Londoño MC, Riveiro-Barciela M, Ahumada A, Muñoz-Gómez R, Roget M, Devesa-Medina MJ, Serra MÁ, et al. Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study. PLoS One. 2019;14(9):e0221567. doi: https://doi.org/10.1371/journal.pone.0221567
Fofiu C, Boeriu A, Coman F, Fofiu A, Panic N, Bulajic M, et al. Interferon-Free Regimen: Equally Effective in Treatment Naive and Experienced HCV Patients. Ann Hepatol. 2019;18(1):137-43. doi: https://doi.org/10.5604/01.3001.0012.7905
Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, et al. Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study. Ther Adv Chronic Dis. 2022;13:20406223211067631. doi: https://doi.org/10.1177/20406223211067631
Rockey DC, Friedman SL. Fibrosis Regression After Eradication of Hepatitis C Virus: From Bench to Bedside. Gastroenterology. 2021;160(5):1502-1520.e1. doi: https://doi.org/10.1053/j.gastro.2020.09.065
Rockey DC. Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies. Clin Gastroenterol Hepatol. 2013;11(3):224-31.e1-5. doi: https://doi.org/10.1016/j.cgh.2013.01.005
Liu X, Xu J, Rosenthal S, Zhang LJ, McCubbin R, Meshgin N, et al. Identification of Lineage-Specific Transcription Factors That Prevent Activation of Hepatic Stellate Cells and Promote Fibrosis Resolution. Gastroenterology. 2020;158(6):1728-1744.e14. doi: https://doi.org/10.1053/j.gastro.2020.01.027
Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2021;18(3):151-66. doi: https://doi.org/10.1038/s41575-020-00372-7
Kawagishi N, Suda G, Kimura M, Maehara O, Shimazaki T, Yamada R, et al. High serum angiopoietin-2 level predicts non-regression of liver stiffness measurement-based liver fibrosis stage after direct-acting antiviral therapy for hepatitis C. Hepatol Res. 2020;50(6):671-81. doi: https://doi.org/10.1111/hepr.13490
Li W, Duan X, Zhu C, Liu X, Jeyarajan AJ, Xu M, et al. Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis through a TGF-β1-Induced OCT4/Nanog Pathway. J Immunol. 2022;208(3):672-84. doi: https://doi.org/10.4049/jimmunol.2001453
Radmanić L, Bodulić K, Šimičić P, Vince A, Lepej SŽ. The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C. Viruses. 2022;14(8):1613. doi: https://doi.org/10.3390/v14081613
Frangogiannis N. Transforming growth factor-β in tissue fibrosis. J Exp Med. 2020;217(3):e20190103. doi: https://doi.org/10.1084/jem.20190103
Soliman H, Ziada D, Salama M, Hamisa M, Badawi R, Hawash N, et al. Predictors for fibrosis regression in chronic HCV patients after the treatment with DAAS: Results of a real-world cohort study. Endocr Metab Immune Disord Drug Targets. 2020;20(1):104-11. doi: https://doi.org/10.2174/1871530319666190826150344
Poordad F, Castro RE, Asatryan A, Aguilar H, Cacoub P, Dieterich D, et al. Long-term safety and efficacy results in hepatitis C virus genotype 1-infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ-I and TOPAZ-II trials. J Viral Hepat. 2020;27(5):497-504. doi: https://doi.org/10.1111/jvh.13261
D'Ambrosio R, Aghemo A, Rumi MG, Ronchi G, Donato MF, Paradis V, et al. A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis. Hepatology. 2012;56(2):532-43. doi: https://doi.org/10.1002/hep.25606
Poynard T, Moussalli J, Munteanu M, Thabut D, Lebray P, Rudler M, et al. Slow regression of liver fibrosis presumed by repeated biomarkers after virological cure in patients with chronic hepatitis C. J Hepatol. 2013;59(4):675-83. doi: https://doi.org/10.1016/j.jhep.2013.05.015
Rout G, Nayak B, Patel AH, Gunjan D, Singh V, Kedia S, et al. Therapy with Oral Directly Acting Agents in Hepatitis C Infection Is Associated with Reduction in Fibrosis and Increase in Hepatic Steatosis on Transient Elastography. J Clin Exp Hepatol. 2019;9(2):207-14. doi: https://doi.org/10.1016/j.jceh.2018.06.009
Prakash S, Rockey DC. 1006 predictors of poor fibrosis regression after direct acting antiviral therapy in patients with chronic hepatitis c and cirrhosis. Gastroenterology. 2020;158(6):1302-3. doi: https://doi.org/10.1016/s0016-5085(20)33918-4
Yoo HW, Park JY, Kim SG, Jung YK, Lee SH, Kim MY, et al. Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents. Sci Rep. 2022;12(1):193. doi: https://doi.org/10.1038/s41598-021-03272-1
Venytska HV, Riabokon OV, Riabokon YY, Shcherbyna RO. Diagnostic values of MMP-9 and TGF-1β in assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C GT 1 infection. Zaporozhye medical journal. 2023;25(4):326-32. doi: https://doi.org/10.14739/2310-1210.2023.4.276462
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